Abstract

Periodontitis, a chronic infection by periodontopathic bacteria, induces uncontrolled inflammation, which leads to periodontal tissue destruction. 2,3,5,4′-Tetrahydroxystilbene-2-O-beta-glucoside (THSG), a polyphenol extracted from Polygoni Multiflori, reportedly has anti-inflammatory properties. In this study, we investigated the mechanisms of THSG on the Porphyromonas gingivalis-induced inflammatory responses in human gingival fibroblasts and animal modeling of ligature-induced periodontitis. Human gingival fibroblast cells were treated with lipopolysaccharide (LPS) extracted from P. gingivalis in the presence of resveratrol or THSG to analyze the expression of TNF-α, IL-1β, and IL-6 genes. Increased AMP-activated protein kinase (AMPK) activation and SirT1 expression were induced by THSG. Treatment of THSG decreased the expression of LPS-induced inflammatory cytokines, enhanced AMPK activation, and increased the expression of SirT1. In addition, it suppressed the activation of NF-κB when cells were stimulated with P. gingivalis LPS. The anti-inflammatory effect of THSG and P. Multiflori crude extracts was reproduced in ligature-induced periodontitis animal modeling. In conclusion, THSG inhibited the inflammatory responses of P. gingivalis-stimulated human gingival fibroblasts and ameliorated ligature-induced periodontitis in animal model.

Highlights

  • Periodontitis is an immune-associated inflammatory disease of the periodontium characterized by progressive destruction of the supporting tissues of teeth [1]

  • Human gingival fibroblasts (HGFs) were refed with medium containing 0.25% stripped fetal bovine serum (FBS) with different concentrations of resveratrol (0, 10, 25, 100, or 200 μM) or THSG (0, 10, 25, 100, or 200 μM) reflashed daily for 72 h

  • Activated nuclear factor E2-related factor (Nrf2) translocates to the nucleus and mediates the transcription of target genes such as heme oxygenase 1 (HO-1) and NAD(P)H:quinine oxidoreductase 1 (NQO-1) which are involved in cellular resistance to oxidative stress which confers protection against inflammation [39]

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Summary

Introduction

Periodontitis is an immune-associated inflammatory disease of the periodontium characterized by progressive destruction of the supporting tissues of teeth [1]. While microbial plaque is the primary etiology and initiates the host immune response, which induces the signs of periodontitis [5], the major component of the Mediators of Inflammation outer membrane of Gram-negative bacteria, Porphyromonas gingivalis, lipopolysaccharide (LPS), initiates the production of various cytokines such as interleukin-8 (IL-8) and TNFα [6] which infiltrate gingival connective tissue and elicit a local inflammatory response. It further causes an increase in number and activity of polymorphonucleocytes (PMN) along with these cytokines. Studies indicate that treatment of rheumatoid arthritis may improve the associated periodontal disease and vice versa [8]

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